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2. A comparison of the McGrath videolaryngoscope with direct laryngoscopy for rapid sequence intubation in the operating theatre: a multicentre randomised controlled trial.

Author

Kriege, M., Lang, P., Lang, C., Schmidtmann, I., Kunitz, O., Roth, M., Strate, M., Schmutz, A., Vits, E., Balogh, O., and Jänig, C.

Subjects
*LARYNGOSCOPES, *LARYNGOSCOPY, *RANDOMIZED controlled trials, *TRACHEA intubation, *INTUBATION, *SURGICAL emergencies
Abstract

Summary: Aspiration of gastric contents is a recognised complication during all phases of anaesthesia. The risk of this event becomes more likely with repeated attempts at tracheal intubation. There is a lack of clinical data on the effectiveness of videolaryngoscopy relative to direct laryngoscopy rapid sequence intubation in the operating theatre. We hypothesised that the use of a videolaryngoscope during rapid sequence intubation would be associated with a higher first pass tracheal intubation success rate than conventional direct laryngoscopy. In this multicentre randomised controlled trial, 1000 adult patients requiring tracheal intubation for elective, urgent or emergency surgery were allocated randomly to airway management using a McGrath™ MAC videolaryngoscope (Medtronic, Minneapolis, MN, USA) or direct laryngoscopy. Both techniques used a Macintosh blade. First‐pass tracheal intubation success was higher in patients allocated to the McGrath group (470/500, 94%) compared with those allocated to the direct laryngoscopy group (358/500, 71.6%), odds ratio (95%CI) 1.31 (1.23–1.39); p < 0.001. This advantage was observed in both trainees and consultants. Cormack and Lehane grade ≥ 3 view occurred less frequently in patients allocated to the McGrath group compared with those allocated to the direct laryngoscopy group (5/500, 1% vs. 94/500, 19%, respectively; p < 0.001). Tracheal intubation with a McGrath videolaryngoscope was associated with a lower rate of adverse events compared with direct laryngoscopy (13/500, 2.6% vs. 61/500, 12.2%, respectively; p < 0.001). These findings suggest that the McGrath videolaryngoscope is superior to a conventional direct laryngoscope for rapid sequence intubation in the operating theatre. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Videolaryngoskopie - immer und überall? Wissenschaftliche Evidenz und aktueller Stellenwert der Videolaryngoskopie in der Anästhesiologie.

Author

Kriege, M.

Subjects
CONTINUING education units, MEDICAL technology, EMERGENCY medical services, LARYNX, LARYNGOSCOPY, TRACHEA intubation, PROFESSIONS, ANESTHESIOLOGY, EVIDENCE-based medicine, AIRWAY (Anatomy), CRITICAL care medicine
Abstract

Copyright of Anaesthesiologie & Intensivmedizin is the property of DGAI e.V. - Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin e.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2024
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5. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Author

Antoniou, AC, Kuchenbaecker, KB, Soucy, P, Beesley, J, Chen, X, McGuffog, L, Lee, A, Barrowdale, D, Healey, S, Sinilnikova, OM, Caligo, MA, Loman, N, Harbst, K, Lindblom, A, Arver, B, Rosenquist, R, Karlsson, P, Nathanson, K, Domchek, S, Rebbeck, T, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Zlowowcka-Perlowska, E, Osorio, A, Duran, M, Andres, R, Benitez, J, Hamann, U, Hogervorst, FB, van Os, TA, Verhoef, S, Meijers-Heijboer, HEJ, Wijnen, J, Garcia, EBG, Ligtenberg, MJ, Kriege, M, Collee, M, Ausems, MGEM, Oosterwijk, JC, Peock, S, Frost, D, Ellis, SD, Platte, R, Fineberg, E, Evans, DG, Lalloo, F, Jacobs, C, Eeles, R, Adlard, J, Davidson, R, Cole, T, Cook, J, Paterson, J, Douglas, F, Brewer, C, Hodgson, S, Morrison, PJ, Walker, L, Rogers, MT, Donaldson, A, Dorkins, H, Godwin, AK, Bove, B, Stoppa-Lyonnet, D, Houdayer, C, Buecher, B, de Pauw, A, Mazoyer, S, Calender, A, Leone, M, Bressac-de Paillerets, B, Caron, O, Sobol, H, Frenay, M, Prieur, F, Ferrer, SF, Mortemousque, I, Buys, S, Daly, M, Miron, A, Terry, MB, Hopper, JL, John, EM, Southey, M, Goldgar, D, Singer, CF, Fink-Retter, A, Tea, M-K, Kaulich, DG, Hansen, TVO, Nielsen, FC, Barkardottir, RB, Gaudet, M, Kirchhoff, T, Joseph, V, Dutra-Clarke, A, Offit, K, and Piedmonte, M

Published
2012

7. S1-Leitlinie Atemwegsmanagement 2023.

Author

Piepho, T., Kriege, M., Byhahn, C., Cavus, E., Dörges, V., Ilper, H., Kehl, F., Loop, T., Raymondos, K., Sujatta, S., Timmermann, A., Zwißler, B., and Noppens, R.

Subjects
MEDICAL masks, INTENSIVE care units, ANESTHESIOLOGY, AIRWAY (Anatomy), CRITICALLY ill, PATIENTS, MEDICAL protocols, RESPIRATORY therapy, DECISION making in clinical medicine, RESUSCITATION, LARYNGOSCOPY, TRACHEA intubation, CAPNOGRAPHY
Abstract

Copyright of Anaesthesiologie & Intensivmedizin is the property of DGAI e.V. - Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin e.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2024
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8. Aktueller Stand von vorhandenen Qualitätsmanagementsystemen in der Anästhesiologie: Vorhaltung und praktische Umsetzung von Qualitätsmanagementsystemen und Sicherheitsprotokollen in der anästhesiologischen Praxis.

Author

Hotz, E., Kitsios, C., and Kriege, M.

Subjects
ANESTHESIA, INDUSTRIAL safety, ACADEMIC medical centers, KEY performance indicators (Management), AIRWAY (Anatomy), HUMAN services programs, MEDICAL protocols, SURVEYS, QUALITY assurance, CLINICAL medicine, DESCRIPTIVE statistics, MANAGEMENT, STATISTICAL sampling, MEDICAL case management
Abstract

Copyright of Anaesthesiologie & Intensivmedizin is the property of DGAI e.V. - Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin e.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2023
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11. A multicentre randomised controlled trial of the McGrath™ Mac videolaryngoscope versus conventional laryngoscopy.

Author

Kriege, M., Noppens, R. R., Turkstra, T., Payne, S., Kunitz, O., Tzanova, I., Schmidtmann, I., Alflen, C., Griemert, E. V., Heid, F., Pirlich, N., Wittenmeier, E., Flier, S., Chui, J., Piepho, T., and Venker, B.

Subjects
*LARYNGOSCOPES, *LARYNGOSCOPY, *RANDOMIZED controlled trials, *TRACHEA intubation, *ELECTIVE surgery
Abstract

Summary: Before completion of this study, there was insufficient evidence demonstrating the superiority of videolaryngoscopy compared with direct laryngoscopy for elective tracheal intubation. We hypothesised that using videolaryngoscopy for routine tracheal intubation would result in higher first‐pass tracheal intubation success compared with direct laryngoscopy. In this multicentre randomised trial, 2092 adult patients without predicted difficult airway requiring tracheal intubation for elective surgery were allocated randomly to either videolaryngoscopy with a Macintosh blade (McGrath™) or direct laryngoscopy. First‐pass tracheal intubation success was higher with the McGrath (987/1053, 94%), compared with direct laryngoscopy (848/1039, 82%); absolute risk reduction (95%CI) was 12.1% (10.9–13.6%). This resulted in a relative risk (95%CI) of unsuccessful tracheal intubation at first attempt of 0.34 (0.26–0.45; p < 0.001) for McGrath compared with direct laryngoscopy. Cormack and Lehane grade ≥ 3 was observed more frequently with direct laryngoscopy (84/1039, 8%) compared with McGrath (8/1053, 0.7%; p < 0.001) No significant difference in tracheal intubation‐associated adverse events was observed between groups. This study demonstrates that using McGrath videolaryngoscopy compared with direct laryngoscopy improves first‐pass tracheal intubation success in patients having elective surgery. Practitioners may consider using this device as first choice for tracheal intubation. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Stellenwert der fiberoptischen Intubation beim erwartet schwierigen Atemweg - Ist der Goldstandard mehr Schein als Sein?

Author

Kriege, M.

Subjects
FIBER optics, THERAPEUTICS, GENERAL anesthesia, CLINICAL competence, LARYNGEAL masks, LARYNGOSCOPY, TRACHEA intubation, VIDEO recording
Abstract

Copyright of Anaesthesiologie & Intensivmedizin is the property of DGAI e.V. - Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin e.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2023
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16. Impact of direct laryngoscopy vs. videolaryngoscopy on signal quality of recurrent laryngeal nerve monitoring in thyroid surgery: a randomised parallel group trial.

Author

Kriege, M., Hilt, J. A., Dette, F., Wittenmeier, E., Meuser, R., Staubitz, J. I., and Musholt, T. J.

Subjects
*LARYNGOSCOPES, *RECURRENT laryngeal nerve, *LARYNGOSCOPY, *THYROID gland, *TRACHEA intubation, *ENDOTRACHEAL tubes, *VOCAL cords
Abstract

Summary: In thyroid surgery, intra‐operative neuromonitoring signals of the recurrent laryngeal nerve can be detected by surface electrodes on a tracheal tube positioned at the vocal fold level. The incidence of difficult tracheal intubation in patients undergoing thyroidectomy for nodular goitre ranges from 5.3% to 20.5%. The aim of this study was to compare videolaryngoscopy with conventional direct laryngoscopy as methods for proper placement of the surface electrode to prevent insufficient intra‐operative nerve signal quality. In this prospective randomised trial, adult patients requiring tracheal intubation during thyroid surgery were randomly allocated to two groups of C‐MAC® (Macintosh style blade) videolaryngoscope or direct laryngoscopy using the Macintosh laryngoscope. Primary outcome was the incidence of insufficient signal electromyogram amplitude level (< 500 μV) after successful tracheal intubation. A total of 260 (130 per group) participants were analysed. An insufficient signal was more frequent with direct laryngoscopy (35/130, 27%), compared with C‐MAC (12/130, 9%, p < 0.001). First‐pass tracheal intubation success rate was lower with direct laryngoscopy (86/130 (66%)) compared with the C‐MAC (125/130 (96%)) (p < 0.0001). Cormack and Lehane grade ≥ 3 was observed more frequently with direct laryngoscopy (16/130 (12%)), compared with the C‐MAC (0/130, (0%)) (p < 0.0001). The results suggest that videolaryngoscopy has an impact on the quality of the initial intra‐operative neuromonitoring signal in patients undergoing thyroid surgery, and this technique can provide optimised surface electrode positioning. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Tumor characteristics and detection method in the MRISC screening program for the early detection of hereditary breast cancer

Author

Kriege, M., Brekelmans, C. T. M., Peterse, H., Obdeijn, I. M., Boetes, C., Zonderland, H. M., Muller, S. H., Kok, T., Manoliu, R. A., Besnard, A. P. E., Tilanus-Linthorst, M. M. A., Seynaeve, C., Bartels, C. C. M., Meijer, S., Oosterwijk, J. C., Hoogerbrugge, N., Tollenaar, R. A. E. M., de Koning, H. J., Rutgers, E. J. T., and Klijn, J. G. M.

Published
2007
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23. Risikofaktoren für laryngeale Intubationsgranulome

Author

Läßig, AK, Nospes, S, Kriege, M, Dette, F, and Musholt, TJ

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund Postoperativ können ausgeprägte Stimmlippeneinblutungen (BL) und Schleimhautschwellungen/Intubationsgranulome (IG) durch ein mechanisches Trauma bei einer endotrachealen Intubation oder prolongierter Beatmungsdauer (meist länger als 24 Stunden), insbesondere bei liegender[zum vollständigen Text gelangen Sie über die oben angegebene URL], 36. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie (DGPP)

Published
2019
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24. The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Author

Terry, MB, Liao, Y, Kast, K, Antoniou, AC, McDonald, JA, Mooij, TM, Engel, C, Nogues, C, Buecher, B, Mari, V, Moretta-Serra, J, Gladieff, L, Luporsi, E, Barrowdale, D, Frost, D, Henderson, A, Brewer, C, Evans, DG, Eccles, D, Cook, J, Ong, K-R, Izatt, L, Ahmed, M, Morrison, PJ, Dommering, CJ, Oosterwijk, JC, Ausems, MGEM, Kriege, M, Buys, SS, Andrulis, IL, John, EM, Daly, M, Friedlander, M, McLachlan, SA, Osorio, A, Caldes, T, Jakubowska, A, Simard, J, Singer, CF, Tan, Y, Olah, E, Navratilova, M, Foretova, L, Gerdes, A-M, Roos-Blom, M-J, Arver, B, Olsson, H, Schmutzler, RK, Hopper, JL, van Leeuwen, FE, Goldgar, D, Milne, RL, Easton, DF, Rookus, MA, Andrieu, N, and EMBRACE, GENEPSO, BCFR, HEBON, kConFab and IBCCS

Subjects
endocrine system diseases, skin and connective tissue diseases
Abstract

Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.

Published
2019

26. The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Author

Terry, M-B. (Mary-beth), Liao, Y.Y., Kast, K. (Karin), Antoniou, A.C. (Antonis), McDonald, JA, Mooij, T.M. (Thea), Engel, C., Nogues, C. (Catherine), Buecher, B. (Bruno), Mari, V., Moretta-Serra, J., Gladieff, L, Luporsi, E., Barrowdale, D. (Daniel), Frost, D. (Debra), Henderson, A, Brewer, C. (C.), Evans, DGR, Eccles, D. (Diana), Cook, J. (Jackie), Ong, K.-R. (Kai-Ren), Izatt, L. (Louise), Ahmed, M., Morrison, P.J. (Patrick), Dommering, C.J. (Charlotte), Oosterwijk, J.C. (Jan), Ausems, M.G.E.M. (Margreet), Kriege, M., Buys, S.S. (Saundra), Andrulis, I.L. (Irene), John, E.M. (Esther), Daly, M.J. (Mark), Friedlander, M. (Michael), McLachlan, SA, Osorio, A. (Ana), Caldes, T. (Trinidad), Jakubowska, A. (Anna), Simard, J. (Jacques), Singer, C.F. (Christian), Tan, Y.H. (Yao Hua), Olah, E., Navratilova, M, Foretova, L. (Lenka), Gerdes, A-M. (Anne-Marie), Roos-Blom, M.J., Arver, B. (Brita Wasteson), Olsson, H. (Hans), Schmutzler, R.K. (Rita), Hopper, J. (John), Leeuwen, F.E. (Flora) van, Goldgar, D. (David), Milne, R.L. (Roger), Easton, D.F. (Douglas), Rookus, M.A. (M.), Andrieu, N, Evans, D.G. (Gareth), Adlard, J.W. (Julian), Eeles, R. (Rosalind), Davidson, R. (Rosemarie), Tischkowitz, M. (Marc), Snape, K., Walker, L.J. (Lisa), Porteous, M.E. (Mary), Donaldson, A. (Alan), Morrison, P, Eason, J. (Jacqueline), Rogers, M, Miller, C, Brady, A, Kennedy, M.J. (John), Barwell, J. (Julian), Gregory, H. (Helen), Pottinger, C. (Caroline), Murray, A. (Anna), Angelakos, M., Dite, G., Tsimiklis, H. (Helen), Breysse, E., Pontois, P., Laborde, L., Stoppa-Lyonnet, D. (Dominique), Gauthier-Villars, M. (Marion), Caron, O. (Olivier), Fourme-Mouret, E., Fricker, J.P. (Jean Pierre), Lasset, C. (Christine), Bonadona, V. (Valérie), Fert-Ferrer, S. (Sandra), Berthet, P. (Pascaline), Vénat-Bouvet, L. (Laurence), Gilbert-Dussardier, B., Faivre, L. (Laurence), Gesta, P., Sobol, H. (Hagay), Eisinger, F. (François), Longy, M. (Michel), Dugast, C., Coupier, I. (Isabelle), Colas, C. (Chrystelle), Soubrier, F., Pujol, P. (Pascal), Corsini, C., Lortholary, A, Vennin, P. (Philippe), Adenis, C., Nguyen, T.D., Penet, C., Delnatte, C.D. (Capucine), Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Demange, L., Dreyfus, H. (Hélène), Cohen-Haguenauer, O. (Odile), Leroux, D. (Dominique), Zattara-Cannoni, H., Bera, O., Hogervorst, F.B.L. (Frans), Adank, M.A. (Muriel), Schmidt, M.K. (Marjanka), Russell, N.S. (Nicola), Jenner, D.J., Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Obdeijn, A.I.M. (Inge-Marie), Asperen, C.J. (Christi) van, Devilee, P. (P.), Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Koudijs, MJ, Aalfs, C.M. (Cora), Engelen, K. (Klaartje) van, Gille, J.J. (Johan), Gómez García, E.B. (Encarna), Blok, M.J.C., Hout, A.H. (Annemarie) van der, Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Siesling, S. (Sabine), Verloop, H. (Herman), Belt-Dusebout, A.W. (Alexandra) van den, Terry, M-B. (Mary-beth), Liao, Y.Y., Kast, K. (Karin), Antoniou, A.C. (Antonis), McDonald, JA, Mooij, T.M. (Thea), Engel, C., Nogues, C. (Catherine), Buecher, B. (Bruno), Mari, V., Moretta-Serra, J., Gladieff, L, Luporsi, E., Barrowdale, D. (Daniel), Frost, D. (Debra), Henderson, A, Brewer, C. (C.), Evans, DGR, Eccles, D. (Diana), Cook, J. (Jackie), Ong, K.-R. (Kai-Ren), Izatt, L. (Louise), Ahmed, M., Morrison, P.J. (Patrick), Dommering, C.J. (Charlotte), Oosterwijk, J.C. (Jan), Ausems, M.G.E.M. (Margreet), Kriege, M., Buys, S.S. (Saundra), Andrulis, I.L. (Irene), John, E.M. (Esther), Daly, M.J. (Mark), Friedlander, M. (Michael), McLachlan, SA, Osorio, A. (Ana), Caldes, T. (Trinidad), Jakubowska, A. (Anna), Simard, J. (Jacques), Singer, C.F. (Christian), Tan, Y.H. (Yao Hua), Olah, E., Navratilova, M, Foretova, L. (Lenka), Gerdes, A-M. (Anne-Marie), Roos-Blom, M.J., Arver, B. (Brita Wasteson), Olsson, H. (Hans), Schmutzler, R.K. (Rita), Hopper, J. (John), Leeuwen, F.E. (Flora) van, Goldgar, D. (David), Milne, R.L. (Roger), Easton, D.F. (Douglas), Rookus, M.A. (M.), Andrieu, N, Evans, D.G. (Gareth), Adlard, J.W. (Julian), Eeles, R. (Rosalind), Davidson, R. (Rosemarie), Tischkowitz, M. (Marc), Snape, K., Walker, L.J. (Lisa), Porteous, M.E. (Mary), Donaldson, A. (Alan), Morrison, P, Eason, J. (Jacqueline), Rogers, M, Miller, C, Brady, A, Kennedy, M.J. (John), Barwell, J. (Julian), Gregory, H. (Helen), Pottinger, C. (Caroline), Murray, A. (Anna), Angelakos, M., Dite, G., Tsimiklis, H. (Helen), Breysse, E., Pontois, P., Laborde, L., Stoppa-Lyonnet, D. (Dominique), Gauthier-Villars, M. (Marion), Caron, O. (Olivier), Fourme-Mouret, E., Fricker, J.P. (Jean Pierre), Lasset, C. (Christine), Bonadona, V. (Valérie), Fert-Ferrer, S. (Sandra), Berthet, P. (Pascaline), Vénat-Bouvet, L. (Laurence), Gilbert-Dussardier, B., Faivre, L. (Laurence), Gesta, P., Sobol, H. (Hagay), Eisinger, F. (François), Longy, M. (Michel), Dugast, C., Coupier, I. (Isabelle), Colas, C. (Chrystelle), Soubrier, F., Pujol, P. (Pascal), Corsini, C., Lortholary, A, Vennin, P. (Philippe), Adenis, C., Nguyen, T.D., Penet, C., Delnatte, C.D. (Capucine), Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Demange, L., Dreyfus, H. (Hélène), Cohen-Haguenauer, O. (Odile), Leroux, D. (Dominique), Zattara-Cannoni, H., Bera, O., Hogervorst, F.B.L. (Frans), Adank, M.A. (Muriel), Schmidt, M.K. (Marjanka), Russell, N.S. (Nicola), Jenner, D.J., Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Obdeijn, A.I.M. (Inge-Marie), Asperen, C.J. (Christi) van, Devilee, P. (P.), Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Koudijs, MJ, Aalfs, C.M. (Cora), Engelen, K. (Klaartje) van, Gille, J.J. (Johan), Gómez García, E.B. (Encarna), Blok, M.J.C., Hout, A.H. (Annemarie) van der, Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Siesling, S. (Sabine), Verloop, H. (Herman), and Belt-Dusebout, A.W. (Alexandra) van den

Abstract

Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95% CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc¼ 0.72, 95% CI ¼ 0.54 to 0.98). Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.

Published
2019

27. Non‐invasive haemoglobin measurement as an index test to detect pre‐operative anaemia in elective surgery patients – a prospective study.

Author

Wittenmeier, E., Paumen, Y., Mildenberger, P., Smetiprach, J., Pirlich, N., Griemert, E.‐V., Kriege, M., and Engelhard, K.

Subjects
HEMOGLOBINS, ELECTIVE surgery, ANEMIA, LONGITUDINAL method, ABSOLUTE value
Abstract

Summary: Non‐invasive haemoglobin measurement using absolute values lacks the precision to be the sole basis for the treatment of pre‐operative anaemia. However, it can possibly serve as a screening test, indexing 'anaemia' with high sensitivity when values remain under prespecified cut‐off values. Based on previous data, non‐invasive haemoglobin cut‐off values (146 g.l−1 for women and 152 g.l−1 for men) detect true anaemia with 99% sensitivity. An index test with these prespecified cut‐off values was verified by prospective measurement of non‐invasive and invasive haemoglobin pre‐operatively in elective surgical patients. In 809 patients, this showed an estimated sensitivity (95%CI) of 98.9% (94.1–99.9%) in women and 96.4% (91.0–99.0%) in men. This saved invasive blood tests in 9% of female and 28% of male patients. In female patients, a lower non‐invasive haemoglobin cut‐off value (138 g.l−1) would save 28% of invasive blood tests with a sensitivity of 95%. The target 99% sensitivity would be reached by non‐invasive haemoglobin cut‐off values of 152 g.l−1 in female and 162 g.l−1 in male patients, saving 3% and 9% of invasive blood tests, respectively. Bias and limits of agreement between non‐invasive and laboratory haemoglobin levels were 2 and − 25 to 28 g.l−1, respectively. Patient and measurement characteristics did not influence the agreement between non‐invasive and laboratory haemoglobin levels. Although sensitivity was very high, the index test using prespecified cut‐off values just failed to reach the target sensitivity to detect true anaemia. Nevertheless, with respect to blood‐sparing effects, the use of the index test in men may be clinically useful, while an index test with a lower cut‐off (132 g.l−1) could be more clinically appropriate in women. [ABSTRACT FROM AUTHOR]

Published
2021
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28. The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Author

Terry, MB, Liao, Y, Kast, K, Antoniou, AC, McDonald, JA, Mooij, TM, Engel, C, Nogues, C, Buecher, B, Mari, V, Moretta-Serra, J, Gladieff, L, Luporsi, E, Barrowdale, D, Frost, D, Henderson, A, Brewer, C, Evans, DG, Eccles, D, Cook, J, Ong, K-R, Izatt, L, Ahmed, M, Morrison, PJ, Dommering, CJ, Oosterwijk, JC, Ausems, MGEM, Kriege, M, Buys, SS, Andrulis, IL, John, EM, Daly, M, Friedlander, M, McLachlan, SA, Osorio, A, Caldes, T, Jakubowska, A, Simard, J, Singer, CF, Tan, Y, Olah, E, Navratilova, M, Foretova, L, Gerdes, A-M, Roos-Blom, M-J, Arver, B, Olsson, H, Schmutzler, RK, Hopper, JL, van Leeuwen, FE, Goldgar, D, Milne, RL, Easton, DF, Rookus, MA, Andrieu, N, Evans, G, Adlard, J, Eeles, R, Davidson, R, Tischkowitz, M, Snape, K, Walker, L, Porteous, M, Donaldson, A, Morrison, P, Eason, J, Rogers, M, Miller, C, Brady, A, Kennedy, MJ, Barwell, J, Gregory, H, Pottinger, C, Murray, A, Angelakos, M, Dite, G, Tsimiklis, H, Breysse, E, Pontois, P, Laborde, L, Stoppa-Lyonnet, D, Gauthier-Villars, M, Caron, O, Fourme-Mouret, E, Fricker, J-P, Lasset, C, Bonadona, V, Fert-Ferrer, S, Berthet, P, Venat-Bouvet, L, Gilbert-Dussardier, B, Faivre, L, Gesta, P, Sobol, H, Eisinger, F, Longy, M, Dugast, C, Coupier, I, Colas, C, Soubrier, F, Pujol, P, Corsini, C, Lortholary, A, Vennin, P, Adenis, C, Tan, DN, Penet, C, Delnatte, C, Tinat, J, Tennevet, I, Limacher, J-M, Maugard, C, Demange, L, Dreyfus, H, Cohen-Haguenauer, O, Leroux, D, Zattara-Cannoni, H, Bera, O, Hogervorst, FBL, Adank, MA, Schmidt, MK, Russell, NS, Jenner, DJ, Collee, JM, van den Ouweland, AMW, Hooning, MJ, Seynaeve, CM, van Deurzen, CHM, Obdeijn, IM, van Asperen, CJ, Devilee, P, Kets, CM, Mensenkamp, AR, Koudijs, MJ, Aalfs, CM, van Engelen, K, Gille, JJP, Gomez-Garcia, EB, Blok, MJ, van der Hout, AH, Mourits, MJ, de Bock, GH, Siesling, S, Verloop, J, van den Belt-Dusebout, AW, Terry, MB, Liao, Y, Kast, K, Antoniou, AC, McDonald, JA, Mooij, TM, Engel, C, Nogues, C, Buecher, B, Mari, V, Moretta-Serra, J, Gladieff, L, Luporsi, E, Barrowdale, D, Frost, D, Henderson, A, Brewer, C, Evans, DG, Eccles, D, Cook, J, Ong, K-R, Izatt, L, Ahmed, M, Morrison, PJ, Dommering, CJ, Oosterwijk, JC, Ausems, MGEM, Kriege, M, Buys, SS, Andrulis, IL, John, EM, Daly, M, Friedlander, M, McLachlan, SA, Osorio, A, Caldes, T, Jakubowska, A, Simard, J, Singer, CF, Tan, Y, Olah, E, Navratilova, M, Foretova, L, Gerdes, A-M, Roos-Blom, M-J, Arver, B, Olsson, H, Schmutzler, RK, Hopper, JL, van Leeuwen, FE, Goldgar, D, Milne, RL, Easton, DF, Rookus, MA, Andrieu, N, Evans, G, Adlard, J, Eeles, R, Davidson, R, Tischkowitz, M, Snape, K, Walker, L, Porteous, M, Donaldson, A, Morrison, P, Eason, J, Rogers, M, Miller, C, Brady, A, Kennedy, MJ, Barwell, J, Gregory, H, Pottinger, C, Murray, A, Angelakos, M, Dite, G, Tsimiklis, H, Breysse, E, Pontois, P, Laborde, L, Stoppa-Lyonnet, D, Gauthier-Villars, M, Caron, O, Fourme-Mouret, E, Fricker, J-P, Lasset, C, Bonadona, V, Fert-Ferrer, S, Berthet, P, Venat-Bouvet, L, Gilbert-Dussardier, B, Faivre, L, Gesta, P, Sobol, H, Eisinger, F, Longy, M, Dugast, C, Coupier, I, Colas, C, Soubrier, F, Pujol, P, Corsini, C, Lortholary, A, Vennin, P, Adenis, C, Tan, DN, Penet, C, Delnatte, C, Tinat, J, Tennevet, I, Limacher, J-M, Maugard, C, Demange, L, Dreyfus, H, Cohen-Haguenauer, O, Leroux, D, Zattara-Cannoni, H, Bera, O, Hogervorst, FBL, Adank, MA, Schmidt, MK, Russell, NS, Jenner, DJ, Collee, JM, van den Ouweland, AMW, Hooning, MJ, Seynaeve, CM, van Deurzen, CHM, Obdeijn, IM, van Asperen, CJ, Devilee, P, Kets, CM, Mensenkamp, AR, Koudijs, MJ, Aalfs, CM, van Engelen, K, Gille, JJP, Gomez-Garcia, EB, Blok, MJ, van der Hout, AH, Mourits, MJ, de Bock, GH, Siesling, S, Verloop, J, and van den Belt-Dusebout, AW

Abstract

BACKGROUND: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. METHODS: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. RESULTS: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). CONCLUSIONS: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.

Published
2018

29. Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade

Author

Purrington, K.S., Slettedahl, S., Bolla, M.K., Michailidou, K., Czene, K., Nevanlinna, H., Bojesen, S.E., Andrulis, I.L., Cox, A., Hall, P., Carpenter, J., Yannoukakos, D., Haiman, C.A., Fasching, P.A., Mannermaa, A., Winqvist, R., Brenner, H., Lindblom, A., Chenevix-Trench, G., Benitez, J., Swerdlow, A., Kristensen, V., Guenel, P., Meindl, A., Darabi, H., Eriksson, M., Fagerholm, R., Aittomaki, K., Blomqvist, C., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Wang, X.S., Olswold, C., Olson, J.E., Mulligan, A.M., Knight, J.A., Tchatchou, S., Reed, M.W.R., Cross, S.S., Liu, J.J., Li, J.M., Humphreys, K., Clarke, C., Scott, R., Fostira, F., Fountzilas, G., Konstantopoulou, I., Henderson, B.E., Schumacher, F., Marchand, L. le, Ekici, A.B., Hartmann, A., Beckmann, M.W., Hartikainen, J.M., Kosma, V.M., Kataja, V., Jukkola-Vuorinen, A., Pylkas, K., Kauppila, S., Dieffenbach, A.K., Stegmaier, C., Arndt, V., Margolin, S., Balleine, R., Perez, J.I.A., Zamora, M.P., Menendez, P., Ashworth, A., Jones, M., Orr, N., Arveux, P., Kerbrat, P., Truong, T., Bugert, P., Toland, A.E., Ambrosone, C.B., Labreche, F., Goldberg, M.S., Dumont, M., Ziogas, A., Lee, E., Dite, G.S., Apicella, C., Southey, M.C., Long, J.R., Shrubsole, M., Deming-Halverson, S., Ficarazzi, F., Barile, M., Peterlongo, P., Durda, K., Jaworska-Bieniek, K., Tollenaar, R.A.E.M., Seynaeve, C., Bruning, T., Ko, Y.D., Deurzen, C.H.M. van, Martens, J.W.M., Kriege, M., Figueroa, J.D., Chanock, S.J., Lissowska, J., Tomlinson, I., Kerin, M.J., Miller, N., Schneeweiss, A., Tapper, W.J., Gerty, S.M., Durcan, L., Mclean, C., Milne, R.L., Baglietto, L., Silva, I.D., Fletcher, O., Johnson, N., Van'T Veer, L.J., Cornelissen, S., Forsti, A., Torres, D., Rudiger, T., Rudolph, A., Flesch-Janys, D., Nickels, S., Weltens, C., Floris, G., Moisse, M., Dennis, J., Wang, Q., Dunning, A.M., Shah, M., Brown, J., Simard, J., Anton-Culver, H., Neuhausen, S.L., Hopper, J.L., Bogdanova, N., Dork, T., Zheng, W., Radice, P., Jakubowska, A., Lubinski, J., Devillee, P., Brauch, H., Hooning, M., Garcia-Closas, M., Sawyer, E., Burwinkel, B., Marmee, F., Eccles, D.M., Giles, G.G., Peto, J., Schmidt, M., Broeks, A., Hamann, U., Chang-Claude, J., Lambrechts, D., Pharoah, P.D.P., Easton, D., Pankratz, V.S., Slager, S., Vachon, C.M., Couch, F.J., ABCTB Investigators, Australian Ovarian Canc Study Grp, kConFab Investigators, GENICA Network, Medical Oncology, Pathology, and Clinical Genetics

Subjects
Oncology, Candidate gene, Fibroblast Growth Factor, amplification, cancer susceptibility loci, Bioinformatics, medicine.disease_cause, Medical and Health Sciences, prostate-cancer, Prostate cancer, Risk Factors, Medizinische Fakultät, Genetics (clinical), Genetics & Heredity, tacc2, Association Studies Articles, Single Nucleotide, General Medicine, Biological Sciences, ddc, risk loci, cell-division, kConFab Investigators, Female, GENICA Network, Type 2, Receptor, Australian Ovarian Cancer Study Group, Breast Neoplasms, Carrier Proteins, Case-Control Studies, Haplotypes, Humans, Neoplasm Staging, Polymorphism, Single Nucleotide, Receptor, Fibroblast Growth Factor, Type 2, Tumor Suppressor Proteins, Genetic Variation, Molecular Biology, Genetics, medicine.medical_specialty, Mitotic index, ABCTB Investigators, Single-nucleotide polymorphism, Biology, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, ddc:610, Polymorphism, Lung cancer, Odds ratio, medicine.disease, genome-wide association, lung-cancer, progression, Carcinogenesis
Abstract

Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 × 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 × 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 × 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer.

Published
2014

30. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3

Author

Hamdi, Y., Soucy, P., Kuchenbaeker, K.B., Pastinen, T., Droit, A., Lemacon, A., Adlard, J., Aittomaki, K., Andrulis, I.L., Arason, A., Arnold, N., Arun, B.K., Azzollini, J., Bane, A., Barjhoux, L., Barrowdale, D., Benitez, J., Berthet, P., Blok, M.J., Bobolis, K., Bonadona, V., Bonanni, B., Bradbury, A.R., Brewer, C., Buecher, B., Buys, S.S., Caligo, M.A., Chiquette, J., Chung, W.K., Claes, K.B., Daly, M.B., Damiola, F., Davidson, R., Hoya, M. de la, Leeneer, K. De, Diez, O., Ding, Y.C., Dolcetti, R., Domchek, S.M., Dorfling, C.M., Eccles, D., Eeles, R., Einbeigi, Z., Ejlertsen, B., Engel, C., Evans, D., Feliubadalo, L., Foretova, L., Fostira, F., Foulkes, W.D., Fountzilas, G., Friedman, E., Frost, D., Ganschow, P., Ganz, P.A., Garber, J., Gayther, S.A., Gerdes, A.M., Glendon, G., Godwin, A.K., Goldgar, D.E., Greene, M.H., Gronwald, J., Hahnen, E., Hamann, U., Hansen, T.V., Hart, S., Hays, J.L., Hogervorst, F.B., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., James, P., Janavicius, R., Jensen, U.B., John, E.M., Joseph, V., Just, W., Kaczmarek, K., Karlan, B.Y., Kets, C.M., Kirk, J., Kriege, M., Laitman, Y., Laurent, M., Lazaro, C., Leslie, G., Lester, J., Lesueur, F., Liljegren, A., Loman, N., Loud, J.T., Manoukian, S., Mariani, M., Mazoyer, S., McGuffog, L., Meijers-Heijboer, H.E., Meindl, A., et al., Hamdi, Y., Soucy, P., Kuchenbaeker, K.B., Pastinen, T., Droit, A., Lemacon, A., Adlard, J., Aittomaki, K., Andrulis, I.L., Arason, A., Arnold, N., Arun, B.K., Azzollini, J., Bane, A., Barjhoux, L., Barrowdale, D., Benitez, J., Berthet, P., Blok, M.J., Bobolis, K., Bonadona, V., Bonanni, B., Bradbury, A.R., Brewer, C., Buecher, B., Buys, S.S., Caligo, M.A., Chiquette, J., Chung, W.K., Claes, K.B., Daly, M.B., Damiola, F., Davidson, R., Hoya, M. de la, Leeneer, K. De, Diez, O., Ding, Y.C., Dolcetti, R., Domchek, S.M., Dorfling, C.M., Eccles, D., Eeles, R., Einbeigi, Z., Ejlertsen, B., Engel, C., Evans, D., Feliubadalo, L., Foretova, L., Fostira, F., Foulkes, W.D., Fountzilas, G., Friedman, E., Frost, D., Ganschow, P., Ganz, P.A., Garber, J., Gayther, S.A., Gerdes, A.M., Glendon, G., Godwin, A.K., Goldgar, D.E., Greene, M.H., Gronwald, J., Hahnen, E., Hamann, U., Hansen, T.V., Hart, S., Hays, J.L., Hogervorst, F.B., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jakubowska, A., James, P., Janavicius, R., Jensen, U.B., John, E.M., Joseph, V., Just, W., Kaczmarek, K., Karlan, B.Y., Kets, C.M., Kirk, J., Kriege, M., Laitman, Y., Laurent, M., Lazaro, C., Leslie, G., Lester, J., Lesueur, F., Liljegren, A., Loman, N., Loud, J.T., Manoukian, S., Mariani, M., Mazoyer, S., McGuffog, L., Meijers-Heijboer, H.E., Meindl, A., and et al.

Abstract

Contains fulltext : 169901.pdf (publisher's version ) (Open Access), PURPOSE: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. METHODS: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. RESULTS: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 x 10-6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. CONCLUSION: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.

Published
2017

31. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3

Author

Hamdi, Y, Soucy, P, Kuchenbaeker, KB, Pastinen, T, Droit, A, Lemacon, A, Adlard, J, Aittomaki, K, Andrulis, IL, Arason, A, Arnold, N, Arun, BK, Azzollini, J, Bane, A, Barjhoux, L, Barrowdale, D, Benitez, J, Berthet, P, Blok, MJ, Bobolis, K, Bonadona, V, Bonanni, B, Bradbury, AR, Brewer, C, Buecher, B, Buys, SS, Caligo, MA, Chiquette, J, Chung, WK, Claes, KBM, Daly, MB, Damiola, F, Davidson, R, De la Hoya, M, De Leeneer, K, Diez, O, Ding, YC, Dolcetti, R, Domchek, SM, Dorfling, CM, Eccles, D, Eeles, R, Einbeigi, Z, Ejlertsen, B, Engel, C, Evans, DG, Feliubadalo, L, Foretova, L, Fostira, F, Foulkes, WD, Fountzilas, G, Friedman, E, Frost, D, Ganschow, P, Ganz, PA, Garber, J, Gayther, SA, Gerdes, A-M, Glendon, G, Godwin, AK, Goldgar, DE, Greene, MH, Gronwald, J, Hahnen, E, Hamann, U, Hansen, TVO, Hart, S, Hays, JL, Hogervorst, FBL, Hulick, PJ, Imyanitov, EN, Isaacs, C, Izatt, L, Jakubowska, A, James, P, Janavicius, R, Jensen, UB, John, EM, Joseph, V, Just, W, Kaczmarek, K, Karlan, BY, Kets, CM, Kirk, J, Kriege, M, Laitman, Y, Laurent, M, Lazaro, C, Leslie, G, Lester, J, Lesueur, F, Liljegren, A, Loman, N, Loud, JT, Manoukian, S, Mariani, M, Mazoyer, S, McGuffog, L, Meijers-Heijboer, HEJ, Meindl, A, Miller, A, Montagna, M, Mulligan, AM, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nussbaum, RL, Olah, E, Olopade, OI, Ong, K-R, Oosterwijk, JC, Osorio, A, Papi, L, Park, SK, Pedersen, IS, Peissel, B, Segura, PP, Peterlongo, P, Phelan, CM, Radice, P, Rantala, J, Rappaport-Fuerhauser, C, Rennert, G, Richardson, A, Robson, M, Rodriguez, GC, Rookus, MA, Schmutzler, RK, Sevenet, N, Shah, PD, Singer, CF, Slavin, TP, Snape, K, Sokolowska, J, Sonderstrup, IMH, Southey, M, Spurdle, AB, Stadler, Z, Stoppa-Lyonnet, D, Sukiennicki, G, Sutter, C, Tan, Y, Tea, M-K, Teixeira, MR, Teule, A, Teo, S-H, Terry, MB, Thomassen, M, Tihomirova, L, Tischkowitz, M, Tognazzo, S, Toland, AE, Tung, N, van den Ouweland, AMW, van der Luijt, RB, van Engelen, K, van Rensburg, EJ, Varon-Mateeva, R, Wappenschmidt, B, Wijnen, JT, Rebbeck, T, Chenevix-Trench, G, Offit, K, Couch, FJ, Nord, S, Easton, DF, Antoniou, AC, Simard, J, Hamdi, Y, Soucy, P, Kuchenbaeker, KB, Pastinen, T, Droit, A, Lemacon, A, Adlard, J, Aittomaki, K, Andrulis, IL, Arason, A, Arnold, N, Arun, BK, Azzollini, J, Bane, A, Barjhoux, L, Barrowdale, D, Benitez, J, Berthet, P, Blok, MJ, Bobolis, K, Bonadona, V, Bonanni, B, Bradbury, AR, Brewer, C, Buecher, B, Buys, SS, Caligo, MA, Chiquette, J, Chung, WK, Claes, KBM, Daly, MB, Damiola, F, Davidson, R, De la Hoya, M, De Leeneer, K, Diez, O, Ding, YC, Dolcetti, R, Domchek, SM, Dorfling, CM, Eccles, D, Eeles, R, Einbeigi, Z, Ejlertsen, B, Engel, C, Evans, DG, Feliubadalo, L, Foretova, L, Fostira, F, Foulkes, WD, Fountzilas, G, Friedman, E, Frost, D, Ganschow, P, Ganz, PA, Garber, J, Gayther, SA, Gerdes, A-M, Glendon, G, Godwin, AK, Goldgar, DE, Greene, MH, Gronwald, J, Hahnen, E, Hamann, U, Hansen, TVO, Hart, S, Hays, JL, Hogervorst, FBL, Hulick, PJ, Imyanitov, EN, Isaacs, C, Izatt, L, Jakubowska, A, James, P, Janavicius, R, Jensen, UB, John, EM, Joseph, V, Just, W, Kaczmarek, K, Karlan, BY, Kets, CM, Kirk, J, Kriege, M, Laitman, Y, Laurent, M, Lazaro, C, Leslie, G, Lester, J, Lesueur, F, Liljegren, A, Loman, N, Loud, JT, Manoukian, S, Mariani, M, Mazoyer, S, McGuffog, L, Meijers-Heijboer, HEJ, Meindl, A, Miller, A, Montagna, M, Mulligan, AM, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Nussbaum, RL, Olah, E, Olopade, OI, Ong, K-R, Oosterwijk, JC, Osorio, A, Papi, L, Park, SK, Pedersen, IS, Peissel, B, Segura, PP, Peterlongo, P, Phelan, CM, Radice, P, Rantala, J, Rappaport-Fuerhauser, C, Rennert, G, Richardson, A, Robson, M, Rodriguez, GC, Rookus, MA, Schmutzler, RK, Sevenet, N, Shah, PD, Singer, CF, Slavin, TP, Snape, K, Sokolowska, J, Sonderstrup, IMH, Southey, M, Spurdle, AB, Stadler, Z, Stoppa-Lyonnet, D, Sukiennicki, G, Sutter, C, Tan, Y, Tea, M-K, Teixeira, MR, Teule, A, Teo, S-H, Terry, MB, Thomassen, M, Tihomirova, L, Tischkowitz, M, Tognazzo, S, Toland, AE, Tung, N, van den Ouweland, AMW, van der Luijt, RB, van Engelen, K, van Rensburg, EJ, Varon-Mateeva, R, Wappenschmidt, B, Wijnen, JT, Rebbeck, T, Chenevix-Trench, G, Offit, K, Couch, FJ, Nord, S, Easton, DF, Antoniou, AC, and Simard, J

Abstract

PURPOSE: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. METHODS: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. RESULTS: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10-6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. CONCLUSION: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.

Published
2017

37. Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

Author

Orr, N., Dudbridge, F., Dryden, N., Maguire, S., Novo, D., Perrakis, E., Johnson, N., Ghoussaini, M., Hopper, J.L., Southey, M.C., Apicella, C., Stone, J., Schmidt, M.K., Broeks, A., Van't Veer, L.J., Hogervorst, F.B., Fasching, P.A., Haeberle, L., Ekici, A.B., Beckmann, M.W., Gibson, L., Aitken, Z., Warren, H., Sawyer, E., Tomlinson, I., Kerin, M.J., Miller, N., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Guenel, P., Truong, T., Cordina-Duverger, E., Sanchez, M., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Benitez, J., Zamora, M.P., Perez, J.I.A., Menendez, P., Anton-Culver, H., Neuhausen, S.L., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Hamann, U., Brauch, H., Justenhoven, C., Bruning, T., Ko, Y.D., Nevanlinna, H., Aittomaki, K., Blomqvist, C., Khan, S., Bogdanova, N., Dork, T., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Chenevix-Trench, G., Beesley, J., Lambrechts, D., Moisse, M., Floris, G., Beuselinck, B., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Radice, P., Peterlongo, P., Peissel, B., Pensotti, V., Couch, F.J., Olson, J.E., Slettedahl, S., Vachon, C., Giles, G.G., Milne, R.L., McLean, C., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Kristensen, V., Alnaes, G.G., Nord, S., Borresen-Dale, A.L., Zheng, W., Deming-Halverson, S., Shrubsole, M., Long, J.R., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C.M., Asperen, C.J. van, Garcia-Closas, M., Figueroa, J., Chanock, S.J., Lissowska, J., Czene, K., Darabi, H., Eriksson, M., Klevebring, D., Hooning, M.J., Hollestelle, A., Deurzen, C.H.M. van, Kriege, M., Hall, P., Li, J.M., Liu, J.J., Humphreys, K., Cox, A., Cross, S.S., Reed, M.W.R., Pharoah, P.D.P., Dunning, A.M., Shah, M., Perkins, B.J., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Ashworth, A., Swerdlow, A., Jones, M., Schoemaker, M.J., Meindl, A., Schmutzler, R.K., Olswold, C., Slager, S., Toland, A.E., Yannoukakos, D., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Matsuo, K., Ito, H., Iwata, H., Ishiguro, J., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Teo, S.H., Yip, C.H., Kang, P., Ikram, M.K., Shu, X.O., Lu, W., Gao, Y.T., Cai, H., Kang, D., Choi, J.Y., Park, S.K., Noh, D.Y., Hartman, M., Miao, H., Lim, W.Y., Lee, S.C., Sangrajrang, S., Gaborieau, V., Brennan, P., McKay, J., Wu, P.E., Hou, M.F., Yu, J.C., Shen, C.Y., Blot, W., Cai, Q.Y., Signorello, L.B., Luccarini, C., Bayes, C., Ahmed, S., Maranian, M., Healey, C.S., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Alvarez, N., Herrero, D., Tessier, D.C., Vincent, D., Bacot, F., Hunter, D.J., Lindstrom, S., Dennis, J., Michailidou, K., Bolla, M.K., Easton, D.F., Silva, I.D., Fletcher, O., Peto, J., GENICA Network, kConFab Investigators, Australian Ovarian Canc Study Grp, Obstetrics & Gynecology, Medical Oncology, Pathology, Ophthalmology, Cardiothoracic Surgery, and Clinical Genetics

Subjects
Asian Continental Ancestry Group, Adult, Hepatocyte Nuclear Factor 3-alpha, Risk, binding, European Continental Ancestry Group, Kruppel-Like Transcription Factors, estrogen-receptor-alpha, Breast Neoplasms, GATA3 Transcription Factor, Polymorphism, Single Nucleotide, White People, Kruppel-Like Factor 4, Asian People, SDG 3 - Good Health and Well-being, Medizinische Fakultät, common variants, expression, Humans, Genetic Predisposition to Disease, ddc:610, Genetic Association Studies, Aged, Association Studies Articles, Estrogen Receptor alpha, Chromosome Mapping, foxa1, Middle Aged, confer susceptibility, analyses reveal, Enhancer Elements, Genetic, risk locus, Genetic Loci, functional variants, genome-wide association, Female, Chromosomes, Human, Pair 9
Abstract

We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis. ispartof: Human Molecular Genetics vol:24 issue:10 pages:2966-84 ispartof: location:England status: published

Published
2015

38. Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers

Author

Zaaijer, L.H., Doorn, H.C. van, Mourits, M.J., Beurden, M. van, Hullu, J.A. de, Adank, M.A., Lonkhuijzen, L.R. van, Vasen, H.F., Slangen, B.F., Gaarenstroom, K.N., Zweemer, R.P., Vencken, P.M., Seynaeve, C., Kriege, M., Zaaijer, L.H., Doorn, H.C. van, Mourits, M.J., Beurden, M. van, Hullu, J.A. de, Adank, M.A., Lonkhuijzen, L.R. van, Vasen, H.F., Slangen, B.F., Gaarenstroom, K.N., Zweemer, R.P., Vencken, P.M., Seynaeve, C., and Kriege, M.

Abstract

Contains fulltext : 171109.pdf (Publisher’s version ) (Open Access), BACKGROUND: It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis. METHODS: We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC. RESULTS: BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HRmult) 1.47; 95% confidence interval (CI) 1.03-2.08 and HRmult 1.43; 95% CI 1.01-2.03), and a non-significantly worse OS (HRmult 1.15; 95% CI 0.84-1.57) and OCSS (HRmult 1.18; 95% CI 0.85-1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HRmult 1.99; 95% CI 1.21-3.31). CONCLUSIONS: Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy.

Published
2016

39. Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers

Author

Zaaijer, L.H. (Leendert H.), Van Doorn, H.C. (Helena C.), Mourits, M.J. (Marjan), Beurden, M. (Marc) van, Hullu, J.A. (Joanne) de, Adank, M.A. (Muriel), Lonkhuijzen, L. van, Vasen, H. (Hans), Slangen, A.H.L. (Arjen), Gaarenstroom, K.N. (Katja), Zweemer, R.P. (Ronald ), Vencken, P.M.L.H. (Peggy), Seynaeve, C.M. (Caroline), Kriege, M. (Mieke), Zaaijer, L.H. (Leendert H.), Van Doorn, H.C. (Helena C.), Mourits, M.J. (Marjan), Beurden, M. (Marc) van, Hullu, J.A. (Joanne) de, Adank, M.A. (Muriel), Lonkhuijzen, L. van, Vasen, H. (Hans), Slangen, A.H.L. (Arjen), Gaarenstroom, K.N. (Katja), Zweemer, R.P. (Ronald ), Vencken, P.M.L.H. (Peggy), Seynaeve, C.M. (Caroline), and Kriege, M. (Mieke)

Abstract

Background:It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis.Methods:We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC.Results:BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HR mult) 1.47; 95% confidence interval (CI) 1.03-2.08 and HR mult 1.43; 95% CI 1.01-2.03), and a non-significantly worse OS (HR mult 1.15; 95% CI 0.84-1.57) and OCSS (HR mult 1.18; 95% CI 0.85-1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HR mult 1.99; 95% CI 1.21-3.31).Conclusions:Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy.

Published
2016
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40. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3

Author

Hamdi, Y. (Yosr), Soucy, P. (Penny), Kuchenbaeker, K.B. (Karoline B.), Pastinen, T. (Tomi), Droit, A. (Arnaud), Lemaçon, A. (Audrey), Adlard, J.W. (Julian), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene), Arason, A. (Adalgeir), Arnold, N. (Norbert), Arun, B.K. (Banu), Azzollini, J., Bane, A.L. (Anita L.), Barjhoux, L. (Laure), Barrowdale, D. (Daniel), Benítez, J. (Javier), Berthet, P. (Pascaline), Blok, M.J. (Marinus), Bobolis, K.A. (Kristie A.), Bonadona, V. (Valérie), Bonnani, B. (Bernardo), Bradbury, A.R. (Angela R.), Brewer, C. (Carole), Buecher, B. (Bruno), Buys, S.S. (Saundra S.), Caligo, M.A. (Maria), Chiquette, J. (Jocelyne), Chung, W. (Wendy), Claes, K.B.M. (Kathleen B.M.), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Davidson, R. (Rosemarie), Hoya, M. (Miguel) de La, De Leeneer, K. (Kim), Díez, O. (Orland), Ding, Y.C. (Yuan), Dolcetti, R. (Riccardo), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Eccles, D. (Diana), Eeles, R. (Ros), Einbeigi, Z. (Zakaria), Ejlertsen, B. (Bent), EMBRACE, Engel, C. (Christoph), Gareth Evans, D., Feliubadaló, L. (L.), Foretova, L. (Lenka), Fostira, F. (Florentia), Foulkes, W.D. (William D.), Fountzilas, G. (George), Friedman, E. (Eitan), Frost, D. (Debra), Ganschow, P. (Pamela), Ganz, P.A. (Patricia A.), Garber, J. (Judy), Gayther, S.A. (Simon), GEMO Study Collaborators, Gerdes, A-M. (Anne-Marie), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Goldgar, D. (David), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Hahnen, E. (Eric), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Hart, S. (Stewart), Hays, J. (John), HEBON, Hogervorst, F.B.L. (Frans), Hulick, P.J. (Peter), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Izatt, L. (Louise), Jakubowska, A. (Anna), James, M. (Margaret), Janavicius, R. (Ramunas), Jensen, U.B., John, E.M. (Esther), Joseph, V. (Vijai), Just, W. (Walter), Kaczmarek, K. (Katarzyna), Karlan, B.Y. (Beth Y.), KConFab Investigators, Kets, C.M. (Marleen), Kirk, J. (Judy), Kriege, M. (Mieke), Laitman, Y. (Yael), Laurent, M. (Maïté), Lázaro, C. (Conxi), Leslie, G. (Goska), Lester, K.J. (Kathryn), Lesueur, F. (Fabienne), Liljegren, A. (Annelie), Loman, N. (Niklas), Loud, J.T. (Jennifer), Manoukian, S. (Siranoush), Mariani, M. (Milena), Mazoyer, S. (Sylvie), McGuffog, L. (Lesley), Meijers-Heijboer, E.J. (Hanne), Meindl, A. (Alfons), Miller, A. (Austin), Montagna, M. (Marco), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nussbaum, R.L. (Robert L.), Olah, E. (Edith), Olopade, O.I. (Olufunmilayo I.), Ong, K.-R. (Kai-Ren), Oosterwijk, J.C. (Jan), Osorio, A. (Ana), Papi, L. (Laura), Park, S.K. (Sue K.), Pedersen, I.S. (Inge Sokilde), Peissel, B. (Bernard), Segura, P.P. (Pedro Perez), Peterlongo, P. (Paolo), Phelan, C. (Catherine), Radice, P. (Paolo), Rantala, J. (Johanna), Rappaport-Fuerhauser, C. (Christine), Rennert, G. (Gad), Richardson, A.L. (Andrea), Robson, M. (Mark), Rodriguez, G.C. (Gustavo), Rookus, M.A. (Matti), Schmutzler, R.K. (Rita), Sevenet, N. (Nicolas), Shah, P.D. (Payal D.), Singer, C.F. (Christian), Slavin, T.P. (Thomas P.), Snape, K. (Katie), Sokolowska, J. (Johanna), Sønderstrup, I.M.H. (Ida Marie Heeholm), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stadler, Z. (Zsofia), Stoppa-Lyonnet, D. (Dominique), Sukiennicki, G. (Grzegorz), Sutter, C. (Christian), Tan, Y. (Yen), Tea, M.-K., Teixeira, P.J., Teulé, A. (A.), Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Tognazzo, S. (Silvia), Toland, A.E. (Amanda), Tung, N. (Nadine), Ouweland, A.M.W. (Ans) van den, Luijt, R.B. (Rob) van der, Engelen, K. (Klaartje) van, Rensburg, E.J. (Elizabeth) van, Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Wijnen, J.T. (Juul), Rebbeck, R. (Timothy), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Couch, F.J. (Fergus J.), Nord, S. (Silje), Easton, D.F. (Douglas F.), Antoniou, A.C. (Antonis), Simard, J. (Jacques), Hamdi, Y. (Yosr), Soucy, P. (Penny), Kuchenbaeker, K.B. (Karoline B.), Pastinen, T. (Tomi), Droit, A. (Arnaud), Lemaçon, A. (Audrey), Adlard, J.W. (Julian), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene), Arason, A. (Adalgeir), Arnold, N. (Norbert), Arun, B.K. (Banu), Azzollini, J., Bane, A.L. (Anita L.), Barjhoux, L. (Laure), Barrowdale, D. (Daniel), Benítez, J. (Javier), Berthet, P. (Pascaline), Blok, M.J. (Marinus), Bobolis, K.A. (Kristie A.), Bonadona, V. (Valérie), Bonnani, B. (Bernardo), Bradbury, A.R. (Angela R.), Brewer, C. (Carole), Buecher, B. (Bruno), Buys, S.S. (Saundra S.), Caligo, M.A. (Maria), Chiquette, J. (Jocelyne), Chung, W. (Wendy), Claes, K.B.M. (Kathleen B.M.), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Davidson, R. (Rosemarie), Hoya, M. (Miguel) de La, De Leeneer, K. (Kim), Díez, O. (Orland), Ding, Y.C. (Yuan), Dolcetti, R. (Riccardo), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Eccles, D. (Diana), Eeles, R. (Ros), Einbeigi, Z. (Zakaria), Ejlertsen, B. (Bent), EMBRACE, Engel, C. (Christoph), Gareth Evans, D., Feliubadaló, L. (L.), Foretova, L. (Lenka), Fostira, F. (Florentia), Foulkes, W.D. (William D.), Fountzilas, G. (George), Friedman, E. (Eitan), Frost, D. (Debra), Ganschow, P. (Pamela), Ganz, P.A. (Patricia A.), Garber, J. (Judy), Gayther, S.A. (Simon), GEMO Study Collaborators, Gerdes, A-M. (Anne-Marie), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Goldgar, D. (David), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Hahnen, E. (Eric), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), Hart, S. (Stewart), Hays, J. (John), HEBON, Hogervorst, F.B.L. (Frans), Hulick, P.J. (Peter), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Izatt, L. (Louise), Jakubowska, A. (Anna), James, M. (Margaret), Janavicius, R. (Ramunas), Jensen, U.B., John, E.M. (Esther), Joseph, V. (Vijai), Just, W. (Walter), Kaczmarek, K. (Katarzyna), Karlan, B.Y. (Beth Y.), KConFab Investigators, Kets, C.M. (Marleen), Kirk, J. (Judy), Kriege, M. (Mieke), Laitman, Y. (Yael), Laurent, M. (Maïté), Lázaro, C. (Conxi), Leslie, G. (Goska), Lester, K.J. (Kathryn), Lesueur, F. (Fabienne), Liljegren, A. (Annelie), Loman, N. (Niklas), Loud, J.T. (Jennifer), Manoukian, S. (Siranoush), Mariani, M. (Milena), Mazoyer, S. (Sylvie), McGuffog, L. (Lesley), Meijers-Heijboer, E.J. (Hanne), Meindl, A. (Alfons), Miller, A. (Austin), Montagna, M. (Marco), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nussbaum, R.L. (Robert L.), Olah, E. (Edith), Olopade, O.I. (Olufunmilayo I.), Ong, K.-R. (Kai-Ren), Oosterwijk, J.C. (Jan), Osorio, A. (Ana), Papi, L. (Laura), Park, S.K. (Sue K.), Pedersen, I.S. (Inge Sokilde), Peissel, B. (Bernard), Segura, P.P. (Pedro Perez), Peterlongo, P. (Paolo), Phelan, C. (Catherine), Radice, P. (Paolo), Rantala, J. (Johanna), Rappaport-Fuerhauser, C. (Christine), Rennert, G. (Gad), Richardson, A.L. (Andrea), Robson, M. (Mark), Rodriguez, G.C. (Gustavo), Rookus, M.A. (Matti), Schmutzler, R.K. (Rita), Sevenet, N. (Nicolas), Shah, P.D. (Payal D.), Singer, C.F. (Christian), Slavin, T.P. (Thomas P.), Snape, K. (Katie), Sokolowska, J. (Johanna), Sønderstrup, I.M.H. (Ida Marie Heeholm), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stadler, Z. (Zsofia), Stoppa-Lyonnet, D. (Dominique), Sukiennicki, G. (Grzegorz), Sutter, C. (Christian), Tan, Y. (Yen), Tea, M.-K., Teixeira, P.J., Teulé, A. (A.), Teo, S.-H. (Soo-Hwang), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tihomirova, L. (Laima), Tischkowitz, M. (Marc), Tognazzo, S. (Silvia), Toland, A.E. (Amanda), Tung, N. (Nadine), Ouweland, A.M.W. (Ans) van den, Luijt, R.B. (Rob) van der, Engelen, K. (Klaartje) van, Rensburg, E.J. (Elizabeth) van, Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Wijnen, J.T. (Juul), Rebbeck, R. (Timothy), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Couch, F.J. (Fergus J.), Nord, S. (Silje), Easton, D.F. (Douglas F.), Antoniou, A.C. (Antonis), and Simard, J. (Jacques)

Abstract

Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of

Published
2016
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41. Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

Author

Darabi, H, Beesley, J, Droit, A, Kar, S, Nord, S, Marjaneh, MM, Soucy, P, Michailidou, K, Ghoussaini, M, Wahl, HF, Bolla, MK, Wang, Q, Dennis, J, Alonso, MR, Andrulis, IL, Anton-Culver, H, Arndt, V, Beckmann, MW, Benitez, J, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Broeks, A, Bruening, T, Burwinkel, B, Chang-Claude, J, Choi, J-Y, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Devilee, P, Doerk, T, Easton, DF, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Galle, E, Garcia-Closas, M, Giles, GG, Goldberg, MS, Gonzalez-Neira, A, Guenel, P, Haiman, CA, Hallberg, E, Hamann, U, Hartman, M, Hollestelle, A, Hopper, JL, Ito, H, Jakubowska, A, Johnson, N, Kang, D, Khan, S, Kosma, V-M, Kriege, M, Kristensen, V, Lambrechts, D, Le Marchand, L, Lee, SC, Lindblom, A, Lophatananon, A, Lubinski, J, Mannermaa, A, Manoukian, S, Margolin, S, Matsuo, K, Mayes, R, Mckay, J, Meindl, A, Milne, RL, Muir, K, Neuhausen, SL, Nevanlinna, H, Olswold, C, Orr, N, Peterlongo, P, Pita, G, Pylkaes, K, Rudolph, A, Sangrajrang, S, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Seynaeve, C, Shah, M, Shen, C-Y, Shu, X-O, Southey, MC, Stram, DO, Surowy, H, Swerdlow, A, Teo, SH, Tessier, DC, Tomlinson, I, Torres, D, Truong, T, Vachon, CM, Vincent, D, Winqvist, R, Wu, AH, Wu, P-E, Yip, CH, Zheng, W, Pharoah, PDP, Hall, P, Edwards, SL, Simard, J, French, JD, Chenevix-Trench, G, Dunning, AM, Darabi, H, Beesley, J, Droit, A, Kar, S, Nord, S, Marjaneh, MM, Soucy, P, Michailidou, K, Ghoussaini, M, Wahl, HF, Bolla, MK, Wang, Q, Dennis, J, Alonso, MR, Andrulis, IL, Anton-Culver, H, Arndt, V, Beckmann, MW, Benitez, J, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Broeks, A, Bruening, T, Burwinkel, B, Chang-Claude, J, Choi, J-Y, Conroy, DM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Devilee, P, Doerk, T, Easton, DF, Fasching, PA, Figueroa, J, Fletcher, O, Flyger, H, Galle, E, Garcia-Closas, M, Giles, GG, Goldberg, MS, Gonzalez-Neira, A, Guenel, P, Haiman, CA, Hallberg, E, Hamann, U, Hartman, M, Hollestelle, A, Hopper, JL, Ito, H, Jakubowska, A, Johnson, N, Kang, D, Khan, S, Kosma, V-M, Kriege, M, Kristensen, V, Lambrechts, D, Le Marchand, L, Lee, SC, Lindblom, A, Lophatananon, A, Lubinski, J, Mannermaa, A, Manoukian, S, Margolin, S, Matsuo, K, Mayes, R, Mckay, J, Meindl, A, Milne, RL, Muir, K, Neuhausen, SL, Nevanlinna, H, Olswold, C, Orr, N, Peterlongo, P, Pita, G, Pylkaes, K, Rudolph, A, Sangrajrang, S, Sawyer, EJ, Schmidt, MK, Schmutzler, RK, Seynaeve, C, Shah, M, Shen, C-Y, Shu, X-O, Southey, MC, Stram, DO, Surowy, H, Swerdlow, A, Teo, SH, Tessier, DC, Tomlinson, I, Torres, D, Truong, T, Vachon, CM, Vincent, D, Winqvist, R, Wu, AH, Wu, P-E, Yip, CH, Zheng, W, Pharoah, PDP, Hall, P, Edwards, SL, Simard, J, French, JD, Chenevix-Trench, G, and Dunning, AM

Abstract

Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10(-09), r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10(-11), r(2) = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

Published
2016

42. Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

Author

Milne, R.L., Burwinkel, B., Michailidou, K., Arias-Perez, J.I., Zamora, M.P., Menendez-Rodriguez, P., Hardisson, D., Mendiola, M., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Dennis, J., Wang, Q., Bolla, M.K., Swerdlow, A., Ashworth, A., Orr, N., Schoemaker, M., Ko, Y.D., Brauch, H., Hamann, U., Andrulis, I.L., Knight, J.A., Glendon, G., Tchatchou, S., Matsuo, K., Ito, H., Iwata, H., Tajima, K., Li, J.M., Brand, J.S., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Lambrechts, D., Peuteman, G., Christiaens, M.R., Smeets, A., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Hartman, M., Hui, M., Lim, W.Y., Chan, C.W., Marme, F., Yang, R.X., Bugert, P., Lindblom, A., Margolin, S., Garcia-Closas, M., Chanock, S.J., Lissowska, J., Figueroa, J.D., Bojesen, S.E., Nordestgaard, B.G., Flyger, H., Hooning, M.J., Kriege, M., Ouweland, A.M.W. van den, Koppert, L.B., Fletcher, O., Johnson, N., Dos-Santos-Silva, I., Peto, J., Zheng, W., Deming-Halverson, S., Shrubsole, M.J., Long, J.R., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Cox, A., Cross, S.S., Reed, M.W.R., Schmidt, M.K., Broeks, A., Cornelissen, S., Braaf, L., Kang, D., Choi, J.Y., Park, S.K., Noh, D.Y., Simard, J., Dumont, M., Goldberg, M.S., Labreche, F., Fasching, P.A., Hein, A., Ekici, A.B., Beckmann, M.W., Radice, P., Peterlongo, P., Azzollini, J., Barile, M., Sawyer, E., Tomlinson, I., Kerin, M., Miller, N., Hopper, J.L., Schmidt, D.F., Makalic, E., Southey, M.C., Teo, S.H., Yip, C.H., Sivanandan, K., Tay, W.T., Shen, C.Y., Hsiung, C.N., Yu, J.C., Hou, M.F., Guenel, P., Truong, T., Sanchez, M., Mulot, C., Blot, W., Cai, Q.Y., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Wu, A.H., Tseng, C.C., Berg, D. van den, Stram, D.O., Bogdanova, N., Dork, T., Muir, K., Lophatananon, A., Stewart-Brown, S., Siriwanarangsan, P., Mannermaa, A., Kataja, V., Kosma, V.M., Hartikainen, J.M., Shu, X.O., Lu, W., Gao, Y.T., Zhang, B., Couch, F.J., Toland, A.E., Yannoukakos, D., Sangrajrang, S., McKay, J., Wang, X.S., Olson, J.E., Vachon, C., Purrington, K., Severi, G., Baglietto, L., Haiman, C.A., Henderson, B.E., Schumacher, F., Marchand, L. le, Devilee, P., Tollenaar, R.A.E.M., Seynaeve, C., Czene, K., Eriksson, M., Humphreys, K., Darabi, H., Ahmed, S., Shah, M., Pharoah, P.D.P., Hall, P., Giles, G.G., Benitez, J., Dunning, A.M., Chenevix-Trench, G., Easton, D.F., GENICA Network, kConFab Investigators, Australian Ovarian Canc Study Grp, TNBCC, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository

Subjects
Adult, Ataxin-7, A Kinase Anchor Proteins, Breast Neoplasms, Nerve Tissue Proteins, Middle Aged, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, Cytoskeletal Proteins, Case-Control Studies, Humans, NIMA-Related Kinases, Female, Genetic Predisposition to Disease, health care economics and organizations, Alleles, Genome-Wide Association Study
Abstract

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility\ud variants, although most studies have been underpowered to detect associations of a realistic magnitude.\ud We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which\ud evidence of association with breast cancer risk had been previously reported. Case-control data were combined\ud from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional\ud logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21\ud [rs1053338, per allele OR 5 1.07, 95% confidence interval (CI) 5 1.04–1.10, P 5 2.9 3 1026\ud ], AKAP9-M463I at\ud 7q21 (rs6964587, OR 5 1.05, 95% CI 5 1.03–1.07, P 5 1.7 3 1026\ud ) and NEK10-L513S at 3p24 (rs10510592,\ud OR 5 1.10, 95% CI 5 1.07 –1.12, P 5 5.1 3 10217). The first two associations reached genome-wide statistical\ud significance in a combined analysis of available data, including independent data from nine genome-wide association\ud studies (GWASs): for ATXN7-K264R, OR 5 1.07 (95% CI 5 1.05–1.10, P 5 1.0 3 1028\ud ); for AKAP9-M463I,\ud OR 5 1.05 (95% CI 5 1.04–1.07, P 5 2.0 3 10210). Further analysis of other common variants in these two\ud regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified\ud a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is\ud associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility\ud region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of\ud the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast\ud cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying\ud variants and the genes through which they act.

Published
2014

43. Genetic Predisposition to In Situ and Invasive Lobular\ud Carcinoma of the Breast

Author

Sawyer, E., Roylance, R., Petridis, C., Brook, M.N., Nowinski, S., Papouli, E., Fletcher, O., Pinder, S., Hanby, A., Kohut, K., Gorman, P., Caneppele, M., Peto, J., Silva, I.D.S., Johnson, N., Swann, R., Dwek, M., Perkins, K-A., Gillett, C., Houlston, R., Ross, G., De Ieso, P., Southey, M.C., Hopper, J.L., Provenzano, E., Apicella, C., Wesseling, J., Cornelissen, S., Keeman, R., Fasching, P.A., Jud, S.M., Ekici, A.B., Beckmann, M.W., Kerin, M.J., Marme, F., Schneeweiss, A., Sohn, C., Burwinkel, B., Guenel, P., Truong, T., Laurent-Puig, P., Kerbrat, P., Bojesen, S.E., Nordestgaard, B.G., Nielsen, S.F., Flyger, H., Milne, R.L., Perez, J.I.A., Menendez, P., Benitez, J., Brenner, H., Dieffenbach, A.K., Arndt, V., Stegmaier, C., Meindl, A., Lichtner, P., Schmutzler, R.K., Lochmann, M., Brauch, H., Fischer, H-P., Ko, Y-D., Nevanlinna, H., Muranen, T.A., Aittomaki, K., Blomqvist, C., Bogdanova, N.V., Dork, T., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V-M., Hartikainen, J.M., Chenevix-Trench, G., Lambrechts, D., Weltens, C., Van Limbergen, E., Hatse, S., Chang-Claude, J., Rudolph, A., Seibold, P., Flesch-Janys, D., Radice, P., Peterlongo, P., Bonanni, B., Volorio, S., Giles, G.G., Severi, G., Baglietto, L., Mclean, C.A., Haiman, C.A., Henderson, B.E., Schumacher, F., Le Marchand, L., Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Kristensen, V., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Kauppila, S., Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Devillee, P., Tollenaar, R.A.E.M., Seynaeve, C.M., Kriege, M., Figueroa, J., Chanock, S.J., Sherman, M.E., Hooning, M.J., Hollestelle, A., van den Ouweland, A.M.W., van Deurzen, C.H.M., Li, J., Czene, K., Humphreys, K., Cox, A., Cross, S.S., Reed, M.W.R., Shah, M., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Swerdlow, A., Ashworth, A., Orr, N., Schoemaker, M., Couch, F.J., Hallberg, E., Gonzalez-Neira, A., Pita, G., Alonso, M.R., Tessier, D.C., Vincent, D., Bacot, F., Bolla, M.K., Wang, Q., Dennis, J., Michailidou, K., Dunning, A.M., Hall, P., Easton, D., Pharoah, P., Schmidt, M.K., Tomlinson, I., Garcia-Closas, M., Network, GENICA, and Investigators, K

Subjects
body regions, skin and connective tissue diseases
Abstract

Invasive lobular breast cancer (ILC) accounts for 10–15% of all invasive breast carcinomas. It is generally ER positive (ER+) and\ud often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common\ud polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To\ud identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure\ud LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/\ud LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses\ud identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09–1.18), P = 6.0610210; P-het for ILC vs IDC\ud ER+ tumors = 1.861024\ud ). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and\ud 15 with LCIS at P,0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, Phet\ud = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/\ud LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences\ud between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11,\ud rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/\ud 14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast\ud cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms\ud predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although\ud there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but\ud distinct etiological pathways within ER+ breast cancer between morphological subtypes.

Published
2014

45. Sensitivity to systemic therapy for metastatic breast cancer in CHEK2 1100delC mutation carriers

Author

Kriege, M. (Mieke), Jager, A. (Agnes), Hollestelle, A. (Antoinette), Berns, P.M.J.J. (Els), Blom, J. (Jannet), Meijer van Gelder, M.E. (Marion), Sieuwerts, A.M. (Anieta), Ouweland, A.M.W. (Ans) van den, Collée, J.M. (Margriet), Kroep, J.R. (Judith), Martens, J.W.M. (John W. M.), Hooning, M.J. (Maartje), Seynaeve, C.M. (Caroline), Kriege, M. (Mieke), Jager, A. (Agnes), Hollestelle, A. (Antoinette), Berns, P.M.J.J. (Els), Blom, J. (Jannet), Meijer van Gelder, M.E. (Marion), Sieuwerts, A.M. (Anieta), Ouweland, A.M.W. (Ans) van den, Collée, J.M. (Margriet), Kroep, J.R. (Judith), Martens, J.W.M. (John W. M.), Hooning, M.J. (Maartje), and Seynaeve, C.M. (Caroline)

Abstract

Purpose: The role of CHEK2 in DNA repair by homologous recombination suggests that CHEK2-associated breast cancer (BC) patients might be more sensitive to chemotherapy inducing double-strand DNA breaks, but results hereon are lacking. We compared the sensitivity to first-line chemotherapy and endocrine therapy between CHEK2 1100delC and non-CHEK2 metastatic breast cancer (MBC) patients. Methods: Sixty-two CHEK2 1100delC MBC patients were selected from three cohorts genotyped for CHEK2 1100delC (one non-BRCA1/2 cohort and two sporadic cohorts). Controls were 62 non-CHEK2 MBC patients, matched for age at and year of primary BC diagnosis, and year of metastatic disease. Objective response rate (complete and partial response) to, and progression-free survival (PFS) and overall survival (OS) after start of first-line chemotherapy and endocrine therapy were compared between CHEK2 and non-CHEK2 patients. Results: Median age at BC diagnosis was 46 and 51 years at MBC diagnosis. First-line chemotherapy consisted of anthracycline-based chemotherapy (n = 73), taxanes (n = 16), CMF(-like) chemotherapy (n = 33) and taxane/anthracycline regimens (n = 2). CHEK2 and non-CHEK2 patients had a comparable objective response rate (44 vs. 52 %). Also, PFS and OS after start of chemotherapy were comparable between both patient groups (hazard ratio 0.91; 95 % confidence interval 0.63–1.30 and 1.03; 95 % CI 0.71–1.49, respectively). Thirty-six CHEK2 and 32 non-CHEK2 patients received first-line endocrine therapy (mainly tamoxifen) for MBC. No significant differences were observed in objective response rate to, and PFS and OS after start of endocrine therapy. Conclusion: No differe

Published
2015
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46. Timing of risk reducing mastectomy in breast cancer patients carrying a BRCA1/2 mutation: retrospective data from the Dutch HEBON study

Author

Wevers, M.R., Schmidt, M.K. (Marjanka), Engelhardt, E.G., Verhoef, S., Hooning, M.J. (Maartje), Kriege, M. (Mieke), Seynaeve, C.M. (Caroline), Collée, J.M. (Margriet), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Koppert, L.B. (Linetta), Witkamp, A.J. (A.), Rutgers, E.J.T. (Emiel), Aaronson, N.K. (Neil), Rookus, M.A. (M.), Ausems, M.G.E.M. (Margreet), Wevers, M.R., Schmidt, M.K. (Marjanka), Engelhardt, E.G., Verhoef, S., Hooning, M.J. (Maartje), Kriege, M. (Mieke), Seynaeve, C.M. (Caroline), Collée, J.M. (Margriet), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Koppert, L.B. (Linetta), Witkamp, A.J. (A.), Rutgers, E.J.T. (Emiel), Aaronson, N.K. (Neil), Rookus, M.A. (M.), and Ausems, M.G.E.M. (Margreet)

Abstract

It is expected that rapid genetic counseling and testing (RGCT) will lead to increasing numbers of breast cancer (BC) patients knowing their BRCA1/2 carrier status before primary surgery. Considering the potential impact of knowing one’s status on uptake and timing of risk-reducing contralateral mastectomy (RRCM), we aimed to evaluate trends over time in RRCM, and differences between carriers identified either before (predictively) or after (diagnostically) diagnosis. We collected data from female BRCA1/2 mutation carriers diagnosed with BC between 1995 and 2009 from four Dutch university hospitals. We compared the timing of genetic testing and RRCM in relation to diagnosis in 1995–2000 versus 2001–2009 for all patients, and predictively and diagnostically tested patients separately. Of 287 patients, 219 (76 %) had a diagnostic BRCA1/2 test. In this cohort, the median time from diagnosis to DNA testing decreased from 28 months for those diagnosed between 1995 and 2000 to 14 months for those diagnosed between 2001 and 2009 (p < 0.001). Similarly, over time women in this cohort underwent RRCM sooner after diagnosis (median of 77 vs. 27 months, p = 0.05). Predictively tested women who subsequently developed BC underwent an immediate RRCM significantly more often than women who had a diagnostic test (21/61, 34 %, vs. 13/170, 7.6 %, p < 0.001). Knowledge of carrying a BRCA1/2 mutation when diagnosed with BC influenced decisions concerning primary surgery. Additionally, in more recent years, women who had not undergone predictive testing were more likely to undergo diagnostic DNA testing and RRCM sooner after diagnosis. This suggests the need for RGCT to guide treatment decisions.

Published
2015
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47. Timing of risk reducing mastectomy in breast cancer patients carrying a BRCA1/2 mutation: retrospective data from the Dutch HEBON study

Author

Genetica Sectie Oncogenetica, Child Health, Cancer, Genetica Klinische Genetica, MS CGO, Wevers, M. R., Schmidt, M. K., Engelhardt, E. G., Verhoef, S., Hooning, M. J., Kriege, M., Seynaeve, C., Collée, M., van Asperen, C. J., Tollenaar, R. A E M, Koppert, L. B., Witkamp, A. J., Rutgers, E. J T, Aaronson, N. K., Rookus, M. A., Ausems, M. G E M, Genetica Sectie Oncogenetica, Child Health, Cancer, Genetica Klinische Genetica, MS CGO, Wevers, M. R., Schmidt, M. K., Engelhardt, E. G., Verhoef, S., Hooning, M. J., Kriege, M., Seynaeve, C., Collée, M., van Asperen, C. J., Tollenaar, R. A E M, Koppert, L. B., Witkamp, A. J., Rutgers, E. J T, Aaronson, N. K., Rookus, M. A., and Ausems, M. G E M

Published
2015

49. Algorithmus zur Sicherung des unerwartet schwierigen Atemwegs : Eine Anwenderanalyse am Simulator.

Author

Ott, T., Truschinski, K., Kriege, M., Naß, M., Herrmann, S., Ott, V., and Sellin, S.

Abstract

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2018
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50. Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

Author

Mavaddat, N., Barrowdale, D., Andrulis, I.L., Domchek, S.M., Eccles, D., Nevanlinna, H., Ramus, S.J., Spurdle, A., Robson, M., Sherman, M., Mulligan, A.M., Couch, F.J., Engel, C., McGuffog, L., Healey, S., Sinilnikova, O.M., Southey, M.C., Terry, M.B., Goldgar, D., O'Malley, F., John, E.M., Janavicius, R., Tihomirova, L., Hansen, T.V.O., Nielsen, F.C., Osorio, A., Stavropoulou, A., Benitez, J., Manoukian, S., Peissel, B., Barile, M., Volorio, S., Pasini, B., Dolcetti, R., Putignano, A.L., Ottini, L., Radice, P., Hamann, U., Rashid, M.U., Hogervorst, F.B., Kriege, M., Luijt, R.B. van der, Peock, S., Frost, D., Evans, D.G., Brewer, C., Walker, L., Rogers, M.T., Side, L.E., Houghton, C., Weaver, J., Godwin, A.K., Schmutzler, R.K., Wappenschmidt, B., Meindl, A., Kast, K., Arnold, N., Niederacher, D., Sutter, C., Deissler, H., Gadzicki, D., Preisler-Adams, S., Varon-Mateeva, R., Schonbuchner, I., Gevensleben, H., Stoppa-Lyonnet, D., Belotti, M., Barjhoux, L., Isaacs, C., Peshkin, B.N., Caldes, T., Hoya, M. de la, Canadas, C., Heikkinen, T., Heikkila, P., Aittomaki, K., Blanco, I., Lazaro, C., Brunet, J., Agnarsson, B.A., Arason, A., Barkardottir, R.B., Dumont, M., Simard, J., Montagna, M., Agata, S., D'Andrea, E., Yan, M., Fox, S., Rebbeck, T.R., Rubinstein, W., Tung, N., Garber, J.E., Wang, X.S., Fredericksen, Z., Pankratz, V.S., Lindor, N.M., Szabo, C., Offit, K., Sakr, R., Gaudet, M.M., Singer, C.F., Tea, M.K., Rappaport, C., Mai, P.L., Greene, M.H., Sokolenko, A., Imyanitov, E., Toland, A.E., Senter, L., Sweet, K., Thomassen, M., Gerdes, A.M., Kruse, T., Caligo, M., Aretini, P., Rantala, J., Wachenfeld, A. von, Henriksson, K., Steele, L., Neuhausen, S.L., Nussbaum, R., Beattie, M., Odunsi, K., Sucheston, L., Gayther, S.A., Nathanson, K., Gross, J., Walsh, C., Karlan, B., Chenevix-Trench, G., Easton, D.F., Antoniou, A.C., HEBON, EMBRACE, GEMO Study Collaborators, kConFab Investigators, SWE-BRCA Collaborators, Consortium Investigators Modifiers, Medical Oncology, Clinical Genetics, MUMC+: DA KG Lab Centraal Lab (9), Genetica & Celbiologie, and RS: GROW - School for Oncology and Reproduction

Subjects
Oncology, Pathology, endocrine system diseases, Epidemiology, Genes, BRCA2, Genes, BRCA1, Estrogen receptor, Gene mutation, 0302 clinical medicine, Cancer screening, Medicine, skin and connective tissue diseases, Estrogen Receptor Status, Ovarian Neoplasms, 0303 health sciences, Middle Aged, female genital diseases and pregnancy complications, 3. Good health, Serous fluid, triple-negative tumors, 030220 oncology & carcinogenesis, Female, estrogen receptor, Adult, medicine.medical_specialty, BRCA1, BRCA2, breast cancer, Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1], Breast Neoplasms, Article, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Translational research [ONCOL 3], Internal medicine, Humans, Genetic Predisposition to Disease, Genetics and epigenetic pathways of disease Translational research [NCMLS 6], Germ-Line Mutation, Aged, 030304 developmental biology, Hereditary cancer and cancer-related syndromes [ONCOL 1], business.industry, Cancer, medicine.disease, Neoplasm Grading, business, Ovarian cancer
Abstract

Background: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. Methods: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers. Results: There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 × 10−5), but increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 × 10−6). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 × 10−13 for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 = 9.4, 95% CI: 7.0–12.6 and PR-positive OR = 1.7, 95% CI: 1.3–2.3, under joint analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95% CI: 2.4–4.4; P = 4.4 × 10−14), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18–0.35; P = 2.3 × 10−15). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%). Conclusions/Impact: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis. Cancer Epidemiol Biomarkers Prev; 21(1); 134–47. ©2011 AACR.

Published
2012

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